Many condensation polymers of formaldehyde and aromatic sulfonic acids have been previously described. For instance, U.S. Pat. No. 4,604,404 discloses the use of such polymers as antiviral agents against the Herpes Simplex virus and HIV infection.
U.S. Pat. No. 5,614,559 discloses that condensation polymers of an aldehyde and aromatic sulfonic acids, such as formaldehyde naphthalene-sulfonic acid condensation polymers, can abrogate HIV gp120 binding to CD4, as demonstrated in CD4/gp120 binding assays. The use of this compound has been shown to be non-cytotoxic and non-inhibitory to antigen induced T lymphocyte proliferation. Based on these findings, these compounds were reported to be useful as therapeutic agents for the treatment and prevention of acquired immunodeficiency syndrome (AIDS), as well as AIDS-related complex (ARC), AIDS-related dementia and non-symptomatic HIV infection.
U.S. Pat. No. 5,958,399 discloses that condensation polymers of aromatic sulfonic acids and an aldehyde, such as naphthalene-sulfonic acid formaldehyde condensation polymers can inhibit or prevent pregnancy. However, none of these references teach or suggest the use of such condensation polymers in preventing or treating papillomavirus (PV) infection and related diseases or conditions.
The papillomaviruses (PVs) are a diverse group of non-enveloped DNA viruses that infect the skin and mucosal tissues of a range of vertebrate species, including humans. Animal PVs occur in a large number of species. Studies have developed bovine PV (BPV) and the Shope cottontail rabbit PV (RCPV) into model systems. Howett et al, A Broad-Spectrum Microbicide with Virucidal Activity Against Sexually Transmitted Viruses, Antimicrobial Agents and Chemotherapy, February 1999, p. 314-321.
Human papillomaviruses (HPVs) are double-stranded DNA viruses, which induce hyperproliferative lesions in epithelial tissues. HPVs cause warts in epithelial target tissues. Common warts of the hands, feet, and genital condylomata all represent common clinical infections of humans. See, Howett et al, supra. A group of genital mucosotropic HPV types are etiologic agents responsible for virtually all cases of cancer of the uterine cervix, as well as a substantial fraction of other ano-genital and head-and-neck cancers. Cancer associated genital HPV types, as well as another set of HPV types associated with the development of benign genital warts, are generally transmitted through sexual contact. Infection with genital HPV types is very common, with an estimated lifetime risk of infection of about 75%. Although most genital HPV infections are subclinical and self-limiting, a subset of persistently infected individuals have lesions that progress to premalignancy or cancer. Buck et al, Carrageenan Is a potent Inhibitor of Papillomavirus Infection, PloS Pathogens, July 2006, Volume 2, Issue 7, e. 69. A portion of persistent HPV infections can progress to invasive cervical cancer. Cervical cancer represents the second most frequent cause of cancer-related deaths in women, accounting for more than 200,000 deaths per year worldwide as of 2001. Christensen et al, Papillomavirus Microbicidal Activities of High-Molecular-Weight Cellulose Sulfate, Dextran Sulfate, and Polysteyrene Sulfonate, Antimicrobial and Chemotherapy, December 2001, p. 3427-3432.
Recent studies have suggested that condoms are, at best, only marginally effective in preventing the sexual transmission of HPV. Although highly effective prophylactic HPV vaccines are expected to become publicly available, they have possible drawbacks. The vaccines are relatively expensive and are likely to be PV type-restricted in their protection. Therefore the vaccines may not initially be available to women in all parts of the world and may not offer protection against all types of cancer-related HPV. See, Buck et al., supra. Compounds with microbicidal activity against papillomaviruses, therefore, may reduce incident infections and decrease the rates of cervical cancer. Thus there is a great need to develop such microbicides.